The long-term goal of this proposal is to test the efficacy of SapC-DOPS: a unique targeting nanotherapeutic for brain tumors, in combination with chemotherapy. Saposin C (SapC) is a sphingolipid activating protein found ubiquitously throughout the body that functions to catabolize glycosphingolipids. SapC preferentially associates with negatively charged phospholipids at an acidic pH. When SapC is coupled with dioleoylphosphatidylserine (DOPS), stable nanovesicles are formed which can selectively fuse with cancer cells, leading to activation of acid sphingomyelinase and subsequent ceramide accumulation, caspase activation, and eventual apoptosis. In this proposal we seek to investigate any synergistic interactions between SapC-DOPS and chemotherapy, which has broad implications on the future treatment paradigms for glioma and other cancers as well.